Cure Alzheimer's Fund - Drug Discoveryhttp://www.curealz.org/taxonomy/term/86
enPromising New Alzheimer’s Drug Validates Anti-Amyloid Approachhttp://www.curealz.org/2015/03/promising-new-alzheimer%E2%80%99s-drug-validates-anti-amyloid-approach
<div class="field field-name-field-image field-type-image field-label-hidden pull-right"><div class="field-items"><div class="field-item even"><img src="http://www.curealz.org/sites/default/files/styles/large/public/stories/Amyloid_plaques_alzheimer_disease_HE_stain.jpg?itok=RP3-XLPL" width="480" height="356" alt="" /></div></div></div><div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"> <p>As <a href="http://www.nytimes.com/2015/03/21/business/alzheimers-drug-trial-shows-cognitive-decline-sharply-slowed.html" target="_blank">reported</a> recently in the <em>New York Times (</em>Business Day, March 20, 2015, “Biogen Reports Its Alzheimer’s Drug Sharply Slows Cognitive Decline”) and other media, the pharmaceutical company Biogen has announced impressive results in a Phase I “human safety” trial of a new drug designed to treat — and possibly prevent — Alzheimer’s disease. The drug, aducanumab, lowered brain Abeta levels and slowed decline in cognitive function compared to a control group of Alzheimer’s patients receiving a placebo.</p><p>“Hats off to Biogen — this is an extremely important breakthrough,” commented <a href="http://curealz.org/people/rudy-tanzi">Rudy Tanzi, Ph.D.</a>, chair of the Cure Alzheimer’s Fund (CAF) Research Consortium. “It is the first trial showing that lowering Abeta levels in the brain can slow down cognitive decline in patients. It also nicely dovetails with several active CAF projects. Most importantly, it further validates our understanding of the disease, from genetic studies, showing that amyloid plaques <em>initiate</em> the disease by causing the formation of neurofibrillary tangles and inflammation. The Biogen study offers the first proof that if you can stop the accumulation of Abeta in the brain, you can slow down or even stop the disease in its tracks.” </p><p>Biogen's new drug is a reproduction of a naturally-occurring human antibody that removes Abeta “plaques” from the brain, potentially stopping the disease from developing any further. If administered early enough, this approach could potentially prevent the development of <em>any</em> Alzheimer’s symptoms. We have known for years that the body produces naturally occurring antibodies to Abeta, called “beta-amyloid auto-antibodies”. In 2005, Dr. Tanzi and <a href="http://curealz.org/people/robert-moir">Dr. Robert Moir</a> at the Massachusetts General Hospital Genetics and Aging Research Unit reported that auto-antibodies naturally made by the body to defend against clumped up aggregates of Abeta are depleted in Alzheimer’s disease. Meanwhile, they appear in higher concentrations in younger unaffected subjects. Based on these findings, Tanzi and Moir proposed in 2005 that since the naturally occurring antibodies were protective against age-related onset of Alzheimer's when present in high concentrations, they could be a powerful therapeutic for treating and preventing Alzheimer’s disease. </p><p>The root studies of the new Biogen therapy, aducanumab, were carried out by their partner, Neurimmune, a Swiss Biotech company. The drug screen was based on seeking out the most potent naturally occurring auto-antibodies against Abeta deposits and then mimicking them to treat the disease. In a very clever approach, the Neurimmune scientists isolated the anti-beta amyloid antibodies from centenarians with remarkably intact cognitive abilities. The assumption was the centenarians were highly protected against Alzheimer's because they possessed potent protective antibodies against Abeta, similar to those described by Moir and Tanzi in 2005. The bet paid off when Neurimmune’s partner, Biogen, announced in the completion of the Phase I clinical trial of 166 patients that their new antibody treatment reduced amyloid levels in the brain and correspondingly slowed down cognitive decline over the course of about one year.</p><p>While the new Biogen therapy shows great promise as it heads directly into a much larger Phase III “efficacy” trial, there are also some concerns, Tanzi noted. “While we are very excited and optimistic about the new Biogen therapy, there is still a lot of work yet to be completed and we cannot just assume that the next trial (Phase III) will be a slam dunk."</p><p>First, the significant cognitive results using the specific memory tests that the FDA bases approval upon, came only from the highest dose group. There were 32 patients in this group versus 40 patients on placebo. “These are still small numbers,” Tanzi said. “so, while we are very hopeful, is not guaranteed that the results will be replicated in the larger Phase III trial."</p><p>Second, the placebo group had a larger decline in cognition over one year than has normally been observed in trials in the past. This may have contributed to a relatively large difference in cognitive decline between the placebo group and the high-dose group. If, in larger trials, the placebo group declines more slowly, it is not guaranteed the treatment groups will attain statistical significance for slowing down cognitive decline.</p><p>Third, there were some side effects, most notably brain swelling and headaches. “These side effects generally resolve on their own over time,” said Tanzi, “but they are a potential concern since they could lead to drop out of patients from future trials”. The side effects were most prevalent in the highest dose group and in carriers of the APOE4 risk gene (present in 60-70% of Alzheimer’s patients).</p><p>CAF has long supported the development of other anti-amyloid treatments, and is several years into a program developing a class of drugs called "gamma-secretase modulators” (GSM) that would also clear amyloid from the brain. While Biogen’s drug would have to be injected and will likely be very expensive, the GSM drug would be taken in a less costly and more convenient pill form. The <a href="http://curealz.org/projects/elucidation-molecular-target-potent-%CE%B3-secretase-modulators">GSM project</a>, led by Tanzi and Steve Wagner, Ph.D, at the University of California at San Diego (UCSD), has been co-funded by CAF and the National Institutes of Health. The investigators hope to get the drug into Phase I trials later this year. </p><p>“This announcement also bodes well for our planned screen of ‘<a href="http://curealz.org/2014/10/%E2%80%9Cgame-changer%E2%80%9D-new-york-times-trumpets-%E2%80%9Cgiant-step-forward%E2%80%9D-tanzi-lab">Alzheimer’s in a Dish</a>’ aimed at finding more anti-amyloid (and anti-tangle) drugs,” said Tanzi. "We have our work cut out for us. But the prospects for our multi-track approach look better than ever thanks to impressive success of the new Biogen trial of aducanumab."</p> </div></div></div><div class="field field-name-field-topics field-type-taxonomy-term-reference field-label-above"><div class="field-label">Keywords:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/taxonomy/term/86">Drug Discovery</a></div></div></div>Mon, 23 Mar 2015 17:49:46 +0000madelson4881 at http://www.curealz.orgAlzstream™ Webinar: From Genes to Therapieshttp://www.curealz.org/2015/02/alzstream%E2%84%A2-webinar-genes-therapies
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</div></div></div><div class="field field-name-field-topics field-type-taxonomy-term-reference field-label-inline clearfix"><div class="field-label">Keywords:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/taxonomy/term/86">Drug Discovery</a></div></div></div>Fri, 06 Feb 2015 16:31:26 +0000madelson4666 at http://www.curealz.orgFeatured Researcher: Charles G. Glabe, Ph.D.http://www.curealz.org/2014/11/featured-researcher-charles-g-glabe-phd
<div class="field field-name-field-image field-type-image field-label-hidden pull-right"><div class="field-items"><div class="field-item even"><img src="http://www.curealz.org/sites/default/files/styles/large/public/stories/Glabe%2CCharlie_RGB.jpg?itok=A-MvKnvz" width="377" height="480" alt="" /></div></div></div><div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"> <p><em>From the age of 2, when he disassembled his brother’s mechanical duck and his father praised him for his curiosity, Charlie Glabe was always interested in the way things work. In college he supported himself as a car mechanic, but found his true passion in scientific research. Today Charlie is a highly respected neuroscientist and a member of the Cure Alzheimer’s Fund Research Consortium.</em></p><p> </p><p><strong>Early days</strong></p><p>Charlie Glabe was born in Columbus, Ohio, the second of three boys. When he was still a baby, his father moved the family to California for a position as a mathematics professor at Sacramento State College. His mother had been a high school English teacher, but after the move decided to stay home with her children.</p><p>In high school, Glabe’s science classes were “kind of bland,” he said. “Girls were much more interesting.” But when he attended Sacramento State College as a biology major, he discovered the joys of science. Glabe worked his way through college as a Volkswagen mechanic, which he now compares to research. “You’re under pressure to get the job done. You need to explore every possibility to figure out what’s wrong, eliminating the easiest things first. And it teaches you humility.” After getting his degree, Glabe wanted to work for the California Fish and Game Commission, but when he didn’t get the job (because he wasn’t a Vietnam war vet), he went to plan B: graduate school. “It turns out that I’m a better scientist than I ever would have been a bureaucrat.”</p><p>In 1973, Glabe attended the University of California’s (UC) graduate program to study cell biology, developmental biology and biochemistry. That’s when he met his wife, a family planning and domestic violence counselor, and built a life that came to include their three grown children. Glabe moved to the East Coast for a few years to become a postdoctoral fellow at The Johns Hopkins University School of Medicine, where he honed his skills as a biochemist. In 1980, he became a postdoctoral fellow at UC, San Francisco, then a staff scientist at the Worcester (Massachusetts) Foundation for Experimental Biology. In 1985, he returned to California as an assistant professor at UC, Irvine.</p><p> </p><p><strong>Alzheimer’s</strong></p><p>Glabe’s big break came later that year when he was working on the biology of marine animals. A friend of his who was working with the noted neuroscientist Carl Cotman asked Glabe for help with a very different experiment. They needed a particular peptide, or protein fragment, for their research. “He had the sequence written down on a piece of paper and said he’d give me $30,000 and a technician salary for a year to make it.” Glabe realized then this was no ordinary peptide; as it happened, he became one of the first people in the world to artificially manufacture Abeta, the famous toxic hallmark of Alzheimer’s disease. “My friend told me that Abeta caused Alzheimer’s and that I should be careful. So I started reading about it, and a light bulb went off in my head. This was something I wanted to work on,” said Glabe. “That’s when I became interested in intercellular amyloid. In 1992, we were looking for a receptor for a beta peptide. I thought it would be easy, but we soon discovered that the long form of Abeta was immortal, while the short form was easily degraded. In the process, we realized that cells could live for a long time despite Abeta accumulation—like a slow-growing tumor that ultimately takes over.”</p><p>In 2007, Glabe received a Cure Alzheimer’s Fund (CAF) grant to produce as many antibodies against Abeta as possible. (One promising strategy to combat Alzheimer’s is to use such antibodies as a vaccine to rid the body of the toxin as it accumulates.) Glabe originally had thought Abeta could fold up in only one way, but he soon discovered it could fold up in many different ways and that different antibodies can recognize and bind to these different <em>foldomers</em>. “This went against all our assumptions,” explained Glabe. “It turned out there were 23 antibodies—many more than we had expected—and we needed to test them right away before they died. I called [Cure Alzheimer’s Fund CEO] Tim Armour to ask for more money and he came through. It turned out that one of these antibodies reacted with a unique type of intranuclear amyloid that had never been seen before.” That finding charted Glabe’s path.</p><p>In 2010, the pharmaceutical giant Eli Lilly ran a clinical trial for Semagacestat, a gamma secretase <em>inhibitor, </em>as the first potentially disease-modifying drug for Alzheimer’s. Rather than helping the test group, the drug actually made them cognitively worse. Many companies working on similar drugs subsequently ended their Alzheimer’s programs, while many dedicated researchers—including Glabe—did a lot of soul searching. “When a drug has the opposite effect that you want it to have,” he said, “the simplest explanation is that we were thinking about the disease mechanism backwards.” He went back to the drawing board and developed a mirror image of the working amyloid hypothesis. “The Eli Lilly drug prevents the secretion of soluble Abeta, and we think that this causes the neuronal retention of insoluble Abeta,” Glabe explained. “These are mirror image mechanisms. When you decrease secreted soluble Abeta, you increase intraneuronal insoluble Abeta. That is the new amyloid hypothesis.”</p><p>His work ultimately supported the idea that gamma secretase <em>modulators </em>would be effective therapeutics vs. gamma secretase <em>inhibitors, </em>which only made patients worse. “You have to be fearless to say that 98 percent of people have been thinking about the disease backwards. But that’s the kind of research Cure Alzheimer’s Fund encourages,” said Glabe. </p><p>These days Charlie spends most of his time in his lab, although he teaches two classes a year. “I love science. I’m addicted to doing experiments and getting results. Everyone who’s part of the Cure Alzheimer’s Fund Research Consortium is doing cutting-edge work. And we have a diverse range of talent that proves that the whole is really greater than the sum of its parts.”</p> </div></div></div><div class="field field-name-field-topics field-type-taxonomy-term-reference field-label-above"><div class="field-label">Keywords:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/taxonomy/term/86">Drug Discovery</a></div></div></div>Fri, 07 Nov 2014 21:48:01 +0000madelson4256 at http://www.curealz.orgThe State of Alzheimer's Research, 2014http://www.curealz.org/2014/10/state-alzheimers-research-2014
<div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"> <p><a href="http://curealz.org/people/rudy-tanzi" target="_blank">Dr. Rudy Tanzi</a>, chairman of the Cure Alzheimer's Fund Research Consortium, presents on the current state of Alzheimer's research. Dr. Tanzi focuses on the importance of the recent "<a href="http://curealz.org/2014/10/%E2%80%9Cgame-changer%E2%80%9D-new-york-times-trumpets-%E2%80%9Cgiant-step-forward%E2%80%9D-tanzi-lab" target="_blank">Alzheimer's in a Dish</a>" study.</p><p>This footage was recorded at our event <a href="http://curealz.org//events/2014/05/2014-fall-symposium-10-years-leading-research" target="_blank">Celebrating 10 Years of Leading Research: 10th Anniversary and Symposium.</a></p> </div></div></div><div class="field field-name-field-video field-type-file field-label-hidden"><div class="field-items"><div class="field-item even"><div class="media-vimeo-video media-vimeo-2">
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</div></div></div><div class="field field-name-field-topics field-type-taxonomy-term-reference field-label-inline clearfix"><div class="field-label">Keywords:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/taxonomy/term/97">Alzheimer&#039;s Causes &amp; Risk Factors</a></div><div class="field-item odd"><a href="/taxonomy/term/86">Drug Discovery</a></div><div class="field-item even"><a href="/taxonomy/term/205">Symposium</a></div><div class="field-item odd"><a href="/taxonomy/term/331">Genes to Therapies™</a></div></div></div>Tue, 21 Oct 2014 20:42:04 +0000madelson4156 at http://www.curealz.orgAn “Inside-Out View” of Alzheimer’s: Study Offers New Take on Amyloid Hypothesishttp://www.curealz.org/2014/08/%E2%80%9Cinside-out-view%E2%80%9D-alzheimer%E2%80%99s-study-offers-new-take-amyloid-hypothesis
<div class="field field-name-field-byline field-type-node-reference field-label-hidden"><div class="field-items"><div class="field-item even"><a href="/people/david-shenk">David Shenk</a></div></div></div><div class="field field-name-field-image field-type-image field-label-hidden pull-right"><div class="field-items"><div class="field-item even"><img src="http://www.curealz.org/sites/default/files/styles/large/public/stories/glabe%20story%20amyloid%20image.jpg?itok=XdfBAvQf" width="480" height="356" alt="" /></div></div></div><div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"> <p class="p1">A new "alternative amyloid hypothesis” from the lab of <a href="http://curealz.org/people/charles-glabe">Dr. Charles Glabe</a>, at the University of California at Irvine, helps explain precisely how neurons (nerve cells) die in Alzheimer’s disease and how known genetic mutations initiate a chain reaction in this long process. The important new hypothesis was driven by research supported by Cure Alzheimer’s Fund, and has just been being published in the Journal <em>Neurobiology of Disease</em>. Dr. Glabe is a longtime member of Cure Alzheimer’s Fund<span style="line-height: 1.42857143;">’</span><span style="line-height: 1.42857143;">s Research Consortium.</span></p><p class="p1">The new approach is an “inside-out view” of Alzheimer’s, according to Glabe. The traditional view is that the protein fragment beta-amyloid aggregates into plaques outside neurons and subsequently causes stress and death to those neurons. Glabe's new hypothesis proposes the reverse order: beta-amyloid forms first within the neuron, causing cell death, which subsequently spurs the formation of neuritic plaques. "It also has therapeutic implications,” he adds. "It suggests that gamma secretase modulators of the type that are being developed by Consortium member <a href="http://curealz.org/people/steven-wagner">Dr. Steven Wagner</a> will be successful because they will increase the secretion of soluble Abeta species and prevent the intraneuronal accumulation that leads to neuron death.” (Find out more about Dr. Wagner's work <a href="http://curealz.org/2014/03/inside-alzheimers-lab-steven-wagner-phd">here</a>.)</p><p class="p1">“This represents an important challenge to our thinking,” says <a href="http://curealz.org/people/rudy-tanzi">Dr. Rudy Tanzi</a>, Chair of the Cure Alzheimer’s Fund Research Consortium. “The amyloid hypothesis has been strongly confirmed in recent years by our genetic and other research. But it’s important that we keep refining it, in order to continually improve intervention strategies.”</p><p class="p2">Read an abstract of the journal article <a href="http://www.ncbi.nlm.nih.gov/pubmed/25092575">here</a>.</p> </div></div></div><div class="field field-name-field-topics field-type-taxonomy-term-reference field-label-above"><div class="field-label">Keywords:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/taxonomy/term/65">Research Updates</a></div><div class="field-item odd"><a href="/taxonomy/term/86">Drug Discovery</a></div></div></div>Thu, 14 Aug 2014 17:50:00 +0000madelson4001 at http://www.curealz.orgAre Brain Cell Regeneration Drugs Ready for Prime Time?http://www.curealz.org/2014/08/are-brain-cell-regeneration-drugs-ready-prime-time
<div class="field field-name-field-byline field-type-node-reference field-label-hidden"><div class="field-items"><div class="field-item even"><a href="/people/david-shenk">David Shenk</a></div></div></div><div class="field field-name-field-image field-type-image field-label-hidden pull-right"><div class="field-items"><div class="field-item even"><img src="http://www.curealz.org/sites/default/files/styles/large/public/stories/gandy%20paper%20image%208.12%20crop.jpg?itok=RXFwO8Ju" width="442" height="220" alt="" /></div></div></div><div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"> <p class="p1">A promising first-in-class drug stimulates the creation of new nerve cells in the brains of Alzheimer's mice and will soon be tested in the brains of human patients, thanks to new research by <a href="http://curealz.org/people/sam-gandy">Dr. Sam Gandy</a>, member of Cure Alzheimer's Fund's Research Consortium, at Mount Sinai School of Medicine in New York.</p><p class="p1">A <a href="http://www.nature.com/mp/journal/v19/n11/full/mp201487a.html" target="_blank">new article</a> by Gandy's team just published in the journal <em>Molecular Psychiatry</em> outlines the extraordinary promise of the drug, known as a "mGluR2/3 blocker". Created by the Japanese pharmaceutical firm Taisho and originally studied for depression, the drug acts by stimulating stem cells in the hippocampus to divide and form new nerve cells. What's more, the learning behavior of the Alzheimer's mice being treated with the mGluR2/3 blocker has been sustained at its normal level, in contrast to the steady decline of the mice not being treated.</p><p class="p1">mGluR2/3 originally caught the attention of Gandy and his team for its possible ability to inhibit production of the toxic protein Abeta42, which is associated with Alzheimer's disease. With funding from Cure Alzheimer's Fund, they conducted a pilot study of the drug's effects on a particular strain of mice. That study turned out such promising results that it has drawn $1 million in funding from the Veterans Administration "MERIT Review" program that supports Gandy's lab at the James J Peters VA Medical Center in the Bronx. Generous additional funding was also provided by the Louis B Mayer Foundation, the Sarah and Gideon Gartner Foundation, and the <a href="http://www.brightfocus.org/alzheimers/newsupdates/new-experimental-drug-class.html" target="_blank">BrightFocus Foundation</a>.</p><p class="p1">The mGluR2/3 blocker has also been administered to healthy young human subjects, and so far has been shown to be safe. The next step for Gandy's team will be to treat elderly human subjects with the drug to test safety in this population before gearing up to test the drug in Alzheimer's disease. With the focus of mainstream Alzheimer's research turning toward prevention, the mGluR2/3 blocker is one of the few drugs that holds promise for repairing brains already damaged by neurodegenerative disease.</p><p class="p1">All of these efforts proceed from the international <a href="http://curealz.org/projects/stem-cell-consortium">Stem Cell Consortium</a> formed by Gandy in 2012 and funded by Cure Alzheimer's Fund. "It's extraordinary that in such a short time, we have moved from ordinary skin cells to induced pluripotent stem cells in a petri dish, to lab-generated human nerve cells, and now to a drug that could potentially create those cells inside a human brain," said Gandy. "We realize that we are unlikely to have much impact in late-stage Alzheimer's, but we are cautiously hopeful that this drug might arrest Alzheimer's disease at an early stage so that patients can remain functional for more extended periods." Gandy's mGluR2/3 blocker is one of five brain cell regenerating agents currently undergoing testing in labs around the world. </p><p class="p1">"We are so proud of this development," said Cure Alzheimer's chairman <a href="http://curealz.org/people/jeffrey-morby">Jeffrey Morby</a>. "Helping incubate cutting edge science that can gain momentum with federal funding -- this is precisely why Cure Alzheimer's Fund exists."</p><p class="p1"> </p><p class="p1"><em>David Shenk is a senior advisor to Cure Alzheimer's Fund and author of </em>The Forgetting: Alzheimer's: Portrait of an Epidemic.</p> </div></div></div><div class="field field-name-field-topics field-type-taxonomy-term-reference field-label-above"><div class="field-label">Keywords:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/taxonomy/term/65">Research Updates</a></div><div class="field-item odd"><a href="/taxonomy/term/86">Drug Discovery</a></div></div></div>Tue, 12 Aug 2014 13:52:40 +0000madelson3986 at http://www.curealz.orgInside the Alzheimer's Lab: Interviews With Our Researchershttp://www.curealz.org/2014/03/inside-alzheimers-lab-interviews-our-researchers
<div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"> <p>Over the past few years, our understanding of Alzheimer’s disease has increased immensely. We can now identify three distinct parts of the disease pathology: early-stage Abeta (amyloid) accumulation, mid-stage development of tau tangles, and late-stage inflammation.</p><p>Scientists on our Research Consortium are investigating all three of these points of intervention. On March 6, we talked to Drs. Steven Wagner, David Holtzman, and Rudy Tanzi about how their labs are working to stop Alzheimer’s in its early, middle, and late stages.</p><p> </p><p><iframe src="http://player.vimeo.com/video/89533690" frameborder="0" width="500" height="281"></iframe></p><p><strong>Early-Stage Intervention: Abeta<br /></strong><strong>Steven Wagner, Ph.D.<br /></strong>University of California, San Diego</p><p>The Abeta protein has long been recognized as central to the development of Alzheimer’s pathology. Only recently, however, have we come realize that this substance not only causes problems in Alzheimer’s patients, but also plays an important role in the innate immune system. Dr. Steven Wagner is working to produce a drug that will modulate an enzyme called gamma secretase, which is a critical contributor to Abeta production. By regulating rather than eliminating Abeta, Wagner and his lab hope to safely halt the development of Alzheimer’s in its early stages.</p><p> </p><p><iframe src="http://player.vimeo.com/video/89533689" frameborder="0" width="500" height="281"></iframe></p><p><strong>Middle-Stage Intervention: Tau<br /></strong><strong>David Holtzman, M.D.<br /></strong>Washington University in St. Louis </p><p>In addition to Abeta, tau tangles, another abnormal aggregation of proteins, are known to cause damage in the Alzheimer’s brain. Dr. Holtzman has recently demonstrated breathtakingly positive results in a proof-of-concept study using antibodies, aimed at stopping the aggregation and spread of tau.</p><p> </p><p><iframe src="http://player.vimeo.com/video/89544887" frameborder="0" width="500" height="281"></iframe></p><p><strong>Late-Stage Intervention: Inflammation<br /></strong><strong>Rudy Tanzi, Ph.D.<br /></strong>Harvard Medical School/Massachusetts General Hospital</p><p>The plaques and tangles of the early and middle stages of Alzheimer’s trigger an immune response, which under normal circumstances would help to clear away damaged and unwanted cells. When the cells responsible (microglia) do not function properly, damaging inflammation occurs – “friendly fire” that greatly exacerbates the disease pathology in a vicious cycle. Dr. Tanzi is researching a gene called CD33 that, when deactivated, helps microglial cells to stop this cycle.</p> </div></div></div><div class="field field-name-field-topics field-type-taxonomy-term-reference field-label-above"><div class="field-label">Keywords:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/taxonomy/term/76">Alzheimer&#039;s therapy</a></div><div class="field-item odd"><a href="/taxonomy/term/86">Drug Discovery</a></div></div></div>Fri, 21 Mar 2014 19:12:29 +0000madelson3598 at http://www.curealz.orgFrancis Collins Addresses Senate on Alzheimer's and Dementiahttp://www.curealz.org/2014/02/francis-collins-addresses-senate-alzheimers-and-dementia
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</div></div></div><div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"> <p>On Wednesday, February 26, 2014, a U.S. Senate subcommittee heard from several panelists on the state of research, funding and awareness for Alzheimer's disease and related dementias. The first panel was led by Dr. Francis Collins, director of the National Institutes of Health (NIH). In his talk, Dr. Collins describes much of the research being conducted by Cure Alzheimer’s Fund, which is focused on identifying both the causes of Alzheimer’s disease and identifying therapeutic targets for drug discovery to prevent cognitive decline. The session served to bring the Alzheimer's crisis to the attention of politicians, as well as to enhance the public's understanding of current research.</p><p>Other presenters at the hearing included Dr. Richard Hodes, director of the National Institute on Aging, and Seth Rogen, actor and founder of Hilarity for Charity, a non-profit raising money for Alzheimer's through comedy events.</p> </div></div></div><div class="field field-name-field-topics field-type-taxonomy-term-reference field-label-above"><div class="field-label">Keywords:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/taxonomy/term/95">Awareness</a></div><div class="field-item odd"><a href="/taxonomy/term/98">Stem Cells</a></div><div class="field-item even"><a href="/taxonomy/term/86">Drug Discovery</a></div></div></div>Thu, 27 Feb 2014 17:23:39 +0000madelson3563 at http://www.curealz.orgDrug Development Strategy: Three Points of Attackhttp://www.curealz.org/2014/01/drug-development-strategy-three-points-attack
<div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"> <p>In view of an emerging consensus on how Alzheimer’s disease develops and progresses, the Cure Alzheimer’s Fund Research Consortium aggressively is focusing on three opportunities for possible intervention—at the early stage of the disease, the middle stage and the late stage. This comprehensive strategy addresses the whole picture of how Alzheimer’s disease develops and progresses, and attacks all three points simultaneously.</p><p> </p><p class="Subhead1"><strong>What we know</strong></p><p>For too long, Alzheimer’s research has been distracted by arguments over “plaques” vs. “tangles.” Some thought the key to treatment was clearing plaques, while others argued that eliminating tangles would cure the disease. Most researchers now agree it is necessary to attack both plaques and tangles, as well as other elements of the pathology, to stop the disease’s progression.</p><p>The Research Consortium now shares the understanding that Alzheimer’s is a vicious cycle of destruction that begins with the production of excessive beta-amyloid peptides (Abeta) that aggregate into clusters called “oligomers,” then proceeds to the creation of tangles from the protein tau that originate inside cells but that recently have been shown to spread to other cells. Both of these create inflammation in the brain, which stimulates more creation of Abeta, thus continuing a cycle that is deadly for brain cells. This destructive cycle can be envisioned as follows:</p><p> </p><h4 class="Subhead1"><strong><img style="float: right; margin-left: 10px; margin-right: 10px;" src="/sites/default/files/stories/2013_Q4Report_simpleDiagram_0.jpg" alt="" width="375" height="827" />Intervention point - A</strong></h4><h4 class="Subhead1"><strong style="font-family: Verdana, sans-serif; font-size: 12px;">Early stage</strong></h4><p>Ideally, this cycle would be stopped at what is thought to be its origin: the overproduction of the protein Abeta. This approach has been pursued broadly for a number of years, so far to little avail. Some drug candidates have proven too toxic; others were ineffective at safe doses. Recent research led by <a href="http://curealz.org/people/robert-moir">Robert Moir, Ph.D.</a>, of Massachusetts General Hospital (MGH) and funded by Cure Alzheimer’s Fund has shown the Abeta protein is an important and integral part of the innate immune system, and therefore maintaining an appropriate balance of the protein rather than eliminating it may be the right therapeutic approach.</p><p>Consortium researchers are pursuing a number of ways to control Abeta production and clearance. Perhaps the most promising research is taking place in the University of California, San Diego lab of <a href="http://curealz.org/people/steven-wagner">Steven Wagner, Ph.D.</a>, and the MGH lab of <a href="http://curealz.org/people/rudy-tanzi">Rudy Tanzi, Ph.D.</a> Their approach has been to develop drugs to modulate an enzyme called gamma secretase, which is a critical contributor to Abeta production. Their effort has been so successful that the compounds they have developed have been adopted by the National Institutes of Health (NIH) as part of its fast-track, high-priority “Blueprint” program.</p><p>“We’re making excellent progress,” reports Wagner. “We have developed a number of compounds and are currently testing them with the hopes of narrowing the list down to one or two clinical candidates.” Tanzi echoes this optimism, saying, “We are hopeful that this project will lead to our gamma secretase modulators in clinical trials over the next year or so.”</p><p> </p><h3 class="Subhead1"><strong>Intervention point - B<br /></strong><strong style="font-family: Verdana, sans-serif; font-size: 12px;">Middle stage</strong></h3><p>In concert with efforts to contain Abeta in the earliest possible stage, consortium members also are pursuing strategies that would zero in on the formation and spread of tau tangles. Foremost among these is the effort led by consortium member <a href="http://curealz.org/people/david-holtzman">David Michael Holtzman, M.D.</a>, based at Washington University in St. Louis, who recently demonstrated breathtakingly positive results in a proof-of-concept study aimed at stopping the aggregation and spread of tau in the middle stages of the disease.</p><p>Holtzman’s study, in collaboration with Washington University’s Marc Diamond, M.D., assembled a variety of potential tau antibodies and introduced them into the brains of genetically engineered mice. Based on a hypothesis that the toxic form of tau gets “spit out” of nerve cells and subsequently “infects” other nearby healthy neurons, the study demonstrated that the antibodies were able to conclusively stop this spreading process; this subsequently led to cognitive improvements in the mice. Their study was published in the journal Neuron in September 2013. The results were “fantastic,” commented the German Center on Degenerative Diseases’ Eckhard Mandelkow, Ph.D., to the Alzheimer’s Research Forum last September. “It explains why antibody therapy might work for tau pathology.”</p><p> </p><h3 class="Subhead1"><strong>Intervention point - C</strong></h3><p class="Subhead2"><strong>Late stage</strong></p><p>Consortium members also are pursuing efforts to curtail Alzheimer’s-related brain inflammation. One of the most promising efforts involves an attempt to inhibit the activity of a gene called CD33. In 2008, Tanzi’s group first discovered this gene’s relationship to late-onset Alzheimer’s in a large family-based, genome-wide association study (GWAS). In 2013, the group described in the journal Neuron the gene’s regulation of immune-response microglial (helper) cells in the aging brain. Microglia normally clear away damaged and unwanted cells in the brain; if they are not functioning properly, damaging inflammation can occur. When Tanzi’s group deactivated CD33 in AD mouse models, more Abeta was cleared away by the microglial cells, leading to diminished amyloid plaque burden and less inflammation. </p><p>The Tanzi lab is attempting to develop effective CD33 inhibitors by screening compounds and antibodies that inhibit CD33 function. The compounds showing the most promise will be tested in AD mouse models. “There’s still some work to do here,” says Tanzi, “but interrupting CD33 could turn out to be a powerful therapeutic strategy.”</p><p> </p><p class="Subhead1"><strong>Following the science</strong></p><p>“We follow the science, wherever it leads,” says Cure Alzheimer’s Fund Chairman Jeffrey Morby. “Alzheimer’s is a complex disease and we’re proud to support our Research Consortium in this multipronged effort to defeat it at each stage.”</p><p> </p><p><em>Want to learn more? David Holtzman, Rudy Tanzi and Steve Wagner will further discuss their research findings in an Alzstream video, moderated by David Shenk, available starting on March 20. The video will be posted at <a href="http://www.curealz.org">www.curealz.org</a> and sent out via e-blast to everyone on our mailing list. If you would like to be added, please let us know at<strong> <a href="mailto:info@curealz.org">info@curealz.org</a></strong>.</em></p> </div></div></div><div class="field field-name-field-topics field-type-taxonomy-term-reference field-label-above"><div class="field-label">Keywords:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/taxonomy/term/86">Drug Discovery</a></div><div class="field-item odd"><a href="/taxonomy/term/75">Alzheimer&#039;s Treatment</a></div></div></div>Tue, 28 Jan 2014 16:02:32 +0000madelson3528 at http://www.curealz.orgDesperate For a Cure: The Search for New Alzheimer's Treatmentshttp://www.curealz.org/2013/10/desperate-cure-search-new-alzheimers-treatments
<div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even"> <p>"Desperate For A Cure: The Search For New Alzheimer's Treatments", a new five-part series by NPR's Sean Corcoran, aired this week on WCAI and will air again next week on WGBH in Boston.</p><p>In each segment, Corcoran discusses current research towards understanding and curing Alzheimer's disease. Among those interviewed are several members of Cure Alzheimer's Fund's Research Consortium, including Robert Moir, Ph.D., Rudy Tanzi, Ph.D, and Steve Wagner, Ph.D. Topics covered range from methods of clearing toxic amyloid beta from the brain to brain scans and challenges regarding upcoming drug trials.</p><p>One constant theme throughout the program is the struggle to find funding for Alzheimer's disease research. "We are not knowledge-constrained; we're budget constrained," says Dr. Rudy Tanzi. He explains that while current drugs in development are promising, pharmaceutical companies are "frustrated now with the failures of the past". The fact that older drugs were not successful in treating AD is making it difficult for new, better drugs to get funded.</p><p>But Corcoran stresses that we don't have time to be so hesitant about new potential therapies. With forecasts of 16 million AD sufferers by 2050, effective treatments are needed more than ever.</p><p>Luckily, some researchers are having success with receiving funding from the National Institutes of Health. Dr. Steve Wagner, whose drug development program was boosted by Cure Alzheimer's Fund back in 2009, is now receiving a 5-year, $1 million-dollar grant from NIH.</p><p>If you'd like to learn more about the exciting research Wagner and others are doing, you can now listen to or read all five segments of "Desperate For A Cure" on <a href="http://capeandislands.org/post/taking-shots-goal-search-new-alzheimers-treatments?nopop=1">WCAI's website</a>.</p> </div></div></div><div class="field field-name-field-topics field-type-taxonomy-term-reference field-label-above"><div class="field-label">Keywords:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/taxonomy/term/86">Drug Discovery</a></div><div class="field-item odd"><a href="/taxonomy/term/75">Alzheimer&#039;s Treatment</a></div><div class="field-item even"><a href="/taxonomy/term/76">Alzheimer&#039;s therapy</a></div></div></div>Fri, 04 Oct 2013 16:46:24 +0000madelson3297 at http://www.curealz.org